CAR-T Regulatory (CAR-Treg) Cells: Engineering and Applications

Regulatory T cells are critical for maintaining immune tolerance. Recent studies have confirmed their therapeutic suppressive potential to modulate immune responses in organ transplant and autoimmune diseases. However, the unknown and nonspecific antigen recognition of polyclonal Tregs has impaired...

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Main Authors: Motahareh Arjomandnejad, Acadia L. Kopec, Allison M. Keeler
Format: Article
Language:English
Published: MDPI AG 2022-01-01
Series:Biomedicines
Subjects:
Online Access:https://www.mdpi.com/2227-9059/10/2/287
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author Motahareh Arjomandnejad
Acadia L. Kopec
Allison M. Keeler
author_facet Motahareh Arjomandnejad
Acadia L. Kopec
Allison M. Keeler
author_sort Motahareh Arjomandnejad
collection DOAJ
description Regulatory T cells are critical for maintaining immune tolerance. Recent studies have confirmed their therapeutic suppressive potential to modulate immune responses in organ transplant and autoimmune diseases. However, the unknown and nonspecific antigen recognition of polyclonal Tregs has impaired their therapeutic potency in initial clinical findings. To address this limitation, antigen specificity can be conferred to Tregs by engineering the expression of transgenic T-cell receptor (TCR) or chimeric antigen receptor (CAR). In contrast to TCR Tregs, CAR Tregs are major histocompatibility complex (MHC) independent and less dependent on interleukin-2 (IL-2). Furthermore, CAR Tregs maintain Treg phenotype and function, home to the target tissue and show enhanced suppressive efficacy compared to polyclonal Tregs. Additional development of engineered CAR Tregs is needed to increase Tregs’ suppressive function and stability, prevent CAR Treg exhaustion, and assess their safety profile. Further understanding of Tregs therapeutic potential will be necessary before moving to broader clinical applications. Here, we summarize recent studies utilizing CAR Tregs in modulating immune responses in autoimmune diseases, transplantation, and gene therapy and future clinical applications.
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spelling doaj.art-866573c17b8e4b23938c0829a29325582023-11-23T18:53:16ZengMDPI AGBiomedicines2227-90592022-01-0110228710.3390/biomedicines10020287CAR-T Regulatory (CAR-Treg) Cells: Engineering and ApplicationsMotahareh Arjomandnejad0Acadia L. Kopec1Allison M. Keeler2Horae Gene Therapy Center, University of Massachusetts Chan Medical School, Worcester, MA 01655, USAHorae Gene Therapy Center, University of Massachusetts Chan Medical School, Worcester, MA 01655, USAHorae Gene Therapy Center, University of Massachusetts Chan Medical School, Worcester, MA 01655, USARegulatory T cells are critical for maintaining immune tolerance. Recent studies have confirmed their therapeutic suppressive potential to modulate immune responses in organ transplant and autoimmune diseases. However, the unknown and nonspecific antigen recognition of polyclonal Tregs has impaired their therapeutic potency in initial clinical findings. To address this limitation, antigen specificity can be conferred to Tregs by engineering the expression of transgenic T-cell receptor (TCR) or chimeric antigen receptor (CAR). In contrast to TCR Tregs, CAR Tregs are major histocompatibility complex (MHC) independent and less dependent on interleukin-2 (IL-2). Furthermore, CAR Tregs maintain Treg phenotype and function, home to the target tissue and show enhanced suppressive efficacy compared to polyclonal Tregs. Additional development of engineered CAR Tregs is needed to increase Tregs’ suppressive function and stability, prevent CAR Treg exhaustion, and assess their safety profile. Further understanding of Tregs therapeutic potential will be necessary before moving to broader clinical applications. Here, we summarize recent studies utilizing CAR Tregs in modulating immune responses in autoimmune diseases, transplantation, and gene therapy and future clinical applications.https://www.mdpi.com/2227-9059/10/2/287CAR Tregautoimmune diseasetransplantationgene therapyengineered Tregs
spellingShingle Motahareh Arjomandnejad
Acadia L. Kopec
Allison M. Keeler
CAR-T Regulatory (CAR-Treg) Cells: Engineering and Applications
Biomedicines
CAR Treg
autoimmune disease
transplantation
gene therapy
engineered Tregs
title CAR-T Regulatory (CAR-Treg) Cells: Engineering and Applications
title_full CAR-T Regulatory (CAR-Treg) Cells: Engineering and Applications
title_fullStr CAR-T Regulatory (CAR-Treg) Cells: Engineering and Applications
title_full_unstemmed CAR-T Regulatory (CAR-Treg) Cells: Engineering and Applications
title_short CAR-T Regulatory (CAR-Treg) Cells: Engineering and Applications
title_sort car t regulatory car treg cells engineering and applications
topic CAR Treg
autoimmune disease
transplantation
gene therapy
engineered Tregs
url https://www.mdpi.com/2227-9059/10/2/287
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AT acadialkopec cartregulatorycartregcellsengineeringandapplications
AT allisonmkeeler cartregulatorycartregcellsengineeringandapplications